Mechanisms underlying mechanical properties of muscle-tendon units

肌肉肌腱单位机械特性的机制

• 批准号: 7524219
• 负责人: Susan V Brooks
• 金额: $ 32.95万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7524219
• 关键词: Accounting; Address; Adult; Aging; Animals; Anterior; Atrophic; Biochemical; Biomechanics; Collagen; Collagen Type I; Collagen Type II; Coupled; Data; Development; Elderly; Environment; Extracellular Matrix; Fiber; Free Radicals; Gene Expression; Glucose; Goals; Individual; Injury; Length; Life; Location; Measurement; Measures; Mechanics; Movement; Muscle; Muscle Fibers; Muscle function; Muscular Atrophy; Optics; Predisposition; Property; Proteins; Proteoglycan; Public Health; Rattus; Rattus norvegicus; Resolution; Role; Series; Skeletal Muscle; Skeletal muscle injury; Speed; Stress; Stretching; Structure; Structure-Activity Relationship; Tendon Injuries; Tendon structure; Time; Tissues; Transforming Growth Factor beta; Variant; Work; age related; aggrecan; base; biglycan; bone; crosslink; decorin; falls; frailty; human TGFB1 protein; improved; middle age; musculoskeletal injury; regional difference; research study; response; versican

DESCRIPTION (provided by applicant): Mechanisms underlying mechanical properties of muscle-tendon units Atrophy, weakness, and injury of skeletal muscle are widely recognized as major contributors to age-related physical frailty, but the importance of changes with aging in extracellular matrix (ECM) of muscle and tendon are poorly understood. Preliminary data show dramatic changes in tendon mechanical properties with aging, with a marked increase in stiffness at the muscle end of the tendon but minimal change at the bone end. The extensive changes with aging in mechanical properties of TA tendons occur with no major change in total collagen content. The regional variation in tendon functional properties coupled with regional variation in underlying structure may contribute to the lack thus far of clear relationships between biochemical and biomechanical properties. Therefore, our goals are to clarify the mechanisms underlying (i) regional differences in mechanical properties along tendons and (ii) changes in mechanical properties with aging, and to determine the impact of tendon changes on muscle function and susceptibility to injury. The working hypotheses are that (i) regional differences in tendon mechanical properties are due to regional variation in collagen content and proteoglycan expression resulting in differences in ECM structure and (ii) with aging, the composition of the entire tendon becomes similar to that of the region nearest bone, causing the tissue to be stiffer and less extensible overall and increasing the likelihood of contraction-induced injury to muscle fibers. Experiments will be performed on tibialis anterior (TA) muscle-tendon units (MTU) and permeabilized single muscle fibers of adult (8 months), middle aged (24 months), and old (33 months) Fisher X Brown Norway rats. The Specific Aims are: 1. determine the impact of aging on passive mechanical properties of MTUs and the interaction between tendon stiffness and muscle fiber length during contraction, 2. elucidate mechanisms underlying the regional differences in mechanical properties along tendons and the changes in tendon mechanical properties that occur with aging, and 3. evaluate the effects of prior active shortening on force deficits caused by lengthening contractions (LCs) of permeabilized single fibers from muscles of adult and old rats. To address the Aims, our approach will be to (i) make high resolution optical measurements of stress-strain relationships along MTUs during stretches without activation and during muscle activation with and without stretch, (ii) perform thorough regional analyses of protein and gene expression, collagen content and cross-linking, and ECM structure of tendons to establish meaningful structure-function relationships, and (iii) apply, to maximally activated permeabilized single fibers from TA muscles of rats, pre-stretch shortening movements that span, in both amplitude and speed, the extension properties of tendons established in Aim 1 to determine the impact on muscle function and susceptibility to injury of alterations in the mechanical environment of fibers that are unavoidably created by changes in tendon properties. PUBLIC HEALTH RELEVANCE. The relevance to public health is based on the impact of increasing susceptibility to muscle and tendon injury as contributors to the development with aging of physical frailty. Frailty causes immobility and falls and is a key factor limiting the ability to live independently. Our project will further understanding of the contribution of changes with aging in the mechanical properties of tendons and muscle fibers to the increased susceptibility to musculoskeletal injury. Clarifying mechanisms underlying changes with aging in the structure and function of muscle-tendon units will improve the likelihood of delaying the onset and progression of frailty.

描述（由申请人提供）：肌肉刺激单位萎缩，骨骼肌肉的萎缩和损伤的机械特性的基础机制被广泛认为是与年龄相关的身体脆弱的主要贡献者，但肌肉外肌肉外基质（ECM和肌腱）的衰老变化的重要性是不足的。初步数据表明，肌腱机械性能随老化的变化发生了巨大变化，并且肌肉末端的刚度显着增加，但在骨头末端的变化很小。 TA肌腱机械性能的衰老发生了广泛的变化，总胶原蛋白含量没有重大变化。肌腱功能特性的区域变化以及潜在结构的区域变化可能导致迄今为止，生化特性和生物力学特性之间缺乏明确的关系。因此，我们的目标是阐明（i）沿肌腱机械性能的区域差异和（ii）随着衰老的衰老机械性能的变化，并确定肌腱变化对肌肉功能的影响和损伤的易感性。工作假设是（i）（i）肌腱机械性能的区域差异是由于胶原蛋白含量和蛋白聚糖表达的区域变化引起的，导致ECM结构和（ii）随着衰老的衰老差异，整个肌腱的组成与最近的骨骼相似，导致组织的炎症和较小的量构成量，并增加了对群体的群体的影响。实验将在胫骨前（TA）肌肉弯曲单元（MTU）和成人（8个月），中年（24个月）和旧（33个月）Fisher X Brown Norway大鼠的前（MTU）和透化的单肌纤维上进行实验。具体目的是：1。确定衰老对MTU的被动机械性能的影响以及肌腱刚度和肌肉纤维长度之间的相互作用，在收缩过程中，阐明了肌腱机械性能的区域差异的基础机制，以及肌腱差异的变化以及对触发的肌腱的变化，以及在抗固定方面发生的频率延长。成年大鼠肌肉的单纤维。 To address the Aims, our approach will be to (i) make high resolution optical measurements of stress-strain relationships along MTUs during stretches without activation and during muscle activation with and without stretch, (ii) perform thorough regional analyses of protein and gene expression, collagen content and cross-linking, and ECM structure of tendons to establish meaningful structure-function relationships, and (iii) apply, to maximally activated permeabilized single fibers from大鼠的Ta肌肉，伸直前缩短运动，在AIM 1中建立的肌腱的延伸特性跨越了肌肉1，以确定对肌肉功能的影响以及对肌腱机械环境中改变的损伤的影响，而纤维的机械环境的变化是不可避免地由肌腱特性变化所产生的。公共卫生相关性。 与公共卫生的相关性是基于增加对肌肉和肌腱损伤的易感性的影响，作为随着身体脆弱的衰老而导致发展的原因。脆弱会导致不动和跌倒，这是限制独立生活能力的关键因素。我们的项目将进一步了解变化在肌腱和肌肉纤维的机械性能中对增加肌肉骨骼损伤的敏感性的贡献。澄清随着肌肉刺激单元的结构和功能的衰老而澄清的机制将改善延迟脆弱的发作和进展的可能性。